Duchenne's muscular dystrophy Flashcards
what is DMD?
severe form of muscular dystrophy
low chance of survival past adolescence
affects skeletal muscles initially and then goes on to affect the heart and diaphragm
inherited condition
pattern of inheritance of DMD?
x-linked recessive condition
what are the causes of DMD?
almost entirely passed on by female carriers as affected males do not normally survive to reproduce
epidemiology
1 in 3500 males
most common of the muscular dystrophies
how is DMD diagnosed?
positive gower's test raised creatinine kinase in serum EMG - detects muscle destruction rather than problems with nerve conduction genetic testing muscle biopsy LFTs - ALT and AST
genetic testing
Xp21 defect
when is DMD diagnosed?
between 5-5.5 years old
what are the symptoms of DMD?
progressive proximal muscle weakness and wasting - most obvious = thigh calf swelling swelling of tongue developmental delay abnormal gait - difficulty standing trouble getting up from chairs unable to walk upstairs waddling gait general motor skill deficits skeletal deformity unable to walk by 10 - need wheelchair cardiomyopathy
what causes calf swelling?
pseudohypertrophy
what causes swelling of the tongue?
fat replacement of wasted muscle
cardiomyopathy in DMD
heart enlargement causing dilated cardiomyopathy
what are the symptoms of dilated cardiomyopathy?
arrhythmia
shortness of breath
fatigue
leg and feet swelling
what are the treatments for DMD?
corticosteroids physiotherapy mechanical ventilation at later stages physical aids occupational therapy ataluren creatine supplements gastrostomy ACE inhibitors and beta blockers for cardiomyopathy pacemaker corrective surgery trial treatments stem cell therapy
corticosteroids
aggressive use sometimes before 10 can convert Duchenne’s to a more Becker’s like prognosis
purpose of physio
reduces rate of contracture and prolongs the useful life of the muscles
physical aids
wheelchair
leg braces
crutches
ataluren
newer drug
for over 5s that can still walk
what do creatine supplements do?
improve muscle strength
what is corrective surgery used for?
scoliosis
ptosis
contractures
scapular fixation
trial treatment
exon skipping
what could stem cell therapy do?
regenerated damaged muscle tissue
pathogenesis
mutation on DMD gene causes lack of dystrophin production, without it there is an excessive calcium entry into the cells, resulting in excess oxidative stress within the cells, damaging the sarcolemma and causing cell death
what does dystrophin do?
part of a structure that connects the cytoskeleton of each muscle fibre to the basal lamina.
why does a raised creatine kinase indicate DMD?
creatine kinase is found within skeletal muscles, brain tissue and cardiac muscle and so it leaks out when muscle cells are damaged as they are broken open and contents are released into the bloodstream
what is the process of genetic testing for DMD?
genetic counselling blood or saliva sample check dystrophin gene CGH array testing MLPA testing PCR southern blot testing sanger gene sequencing can be done prenatally
prenatal genetic testing
non-invasive prenatal diagnosis chorion villus sampling amniocentesis placental biopsy foetal blood sampling
MLPA
multiplex ligation-dependent probe amplification
CGH
comparative genomic hybridisation
genetic testing
prenatal if parents are carriers
needed if you are offered genetic test
can be directed to relevant patient support groups
genetic testing is free if you are referred for it by a hospital specialist
discussion about risk, prognosis, consequences, tests available
